In congestive heart failure (CHF), the sympathetic nervous system is activated even at rest and the mechanisms of exercise-induced sympathoexcitation are poorly defined. In this study, the responses of sympathetic nerve activity directed to muscle (MSNA) and to skin (SSNA, peroneal microneurography) during rhythmic handgrip (RHG) at 25% of maximal voluntary contraction and post-handgrip circulatory arrest (PHG-CA) in CHF are compared to those of an age-matched control group. During RHG, the CHF patients fatigued prematurely. At end exercise, the increase in MSNA was similar in both groups. However, while MSNA returned to baseline in the controls during PHG-CA, it remained elevated in CHF. Similarly, at end exercise, the increase in SSNA was comparable in both groups while SSNA remained elevated during PHG-CA in CHF but not in the controls. In a separate control group, even high intensity static handgrip was not accompanied by maintained elevation of SSNA during PHG-CA. Nuclear magnetic resonance spectroscopy during RHG demonstrated significant muscle acidosis and accumulation of inorganic phosphate in CHF but not in controls. We conclude that in CHF rhythmic hand grip leads to premature fatigue and accumulation of muscle metabolites. The prominent PHG-CA response of MSNA and SSNA in CHF suggests activation of the muscle metaboreflex. Because in contrast to controls, in CHF both MSNA and SSNA appear to be under muscle metaboreflex control, the mechanisms and distribution of sympathoexcitation during exercise appear to be different from normal.